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Journal of Molecular Biology

Faraz M Harsini, Anthony A Bui, Anne M Rice, Sukanya Chebrolu, Kerry L Fuson, Andrei Turtoi, Mazdak Bradberry, Edwin R Chapman, R Bryan Sutton
Dysferlin has been implicated in acute membrane repair processes, whereas myoferlin's activity is maximal during the myoblast fusion stage of early skeletal muscle cell development. Both proteins are similar in size and domain structure; however, despite the overall similarity, myoferlin's known physiological functions do not overlap with those of dysferlin. Here we present for the first time the X-ray crystal structure of human myoferlin C2A to 1.9 Å̊ resolution bound to two divalent cations, and compare its 3D structure and membrane binding activities to that of dysferlin C2A...
April 17, 2019: Journal of Molecular Biology
Anastasiya Shulman, Michael Katz, Hadas Cohen-Dvashi, Harry M Greenblatt, Yaakov Levy, Ron Diskin
Lassa virus (LASV) is a notorious human pathogen in West Africa. Its class-I trimeric spike complex displays a distinct architecture, and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2LASV ) in its post-fusion conformation. GP2LASV adopts a canonical helical bundle configuration similarly to other viruses in its family. The core packing of GP2LASV however, is more organized compared to GP2 from other viruses reducing the formation of internal hydrophobic cavities...
April 17, 2019: Journal of Molecular Biology
Nicole J De Nisco, Michael Neugent, Jason Mull, Luming Chen, Amy Kuprasertkul, Marcela de Souza Santos, Kelli L Palmer, Philippe Zimmern, Kim Orth
Urinary tract infections (UTIs) are the most commonly reported infections in adult women and have high rates of recurrence, especially in postmenopausal women. Recurrent UTI (RUTI) greatly reduces quality of life, places a significant burden on the healthcare system, and contributes to antimicrobial resistance. Because treatment of RUTI by long-term antibiotic therapy is often ineffective or poorly tolerated in elderly women, new therapies must be developed. The molecular basis of RUTI, especially in postmenopausal women, has remained unclear because modeling RUTI in mice is difficult, and human data are limited...
April 16, 2019: Journal of Molecular Biology
Douglas F Browning, Matej Butala, Stephen J W Busby
Transcription in most bacteria is tightly regulated in order to facilitate bacterial adaptation to different environments, and transcription factors play a key role in this. Here we give a brief overview of the essential features of bacterial transcription factors and how they affect transcript initiation at target promoters. We focus on complex promoters that are regulated by combinations of activators and repressors, combinations of repressors only, or combinations of activators. At some promoters, transcript initiation is regulated by nucleoid-associated proteins, which often work together with transcription factors...
April 15, 2019: Journal of Molecular Biology
Aikaterini C Tsika, Efstathios Melekis, Sofia-Antigoni Tsatsouli, Nicolas Papageorgiou, Maria J Maté, Bruno Canard, Bruno Coutard, Detlef Bentrop, Georgios A Spyroulias
Mayaro virus (MAYV) is a member of Togaviridae family which also includes Chikungunya virus as a notorious member. MAYV recently emerged in urban areas of the Americas, and this emergence emphasized the current paucity of knowledge about its replication cycle. The macro domain (MD) of MAYV belongs to the N-terminal region of its non-structural protein 3, part of the replication complex. Here, we report the first structural and dynamical characterization of a previously unexplored Alphavirus macro domain investigated through high resolution NMR spectroscopy, along with data on its ligand selectivity and binding properties...
April 15, 2019: Journal of Molecular Biology
Honorata Czapinska, Wojciech Siwek, Roman H Szczepanowski, Janusz M Bujnicki, Matthias Bochtler, Krzysztof J Skowronek
Specificity engineering is challenging, and particularly difficult for enzymes that have the catalytic machinery and specificity determinants in close proximity. Restriction endonucleases have been used as a paradigm for protein engineering, but successful cases are rare. Here, we present the results of a directed evolution approach to the engineering of a dimeric, blunt end cutting restriction enzyme NlaIV (GGN/NCC). Based on the remote similarity to EcoRV endonuclease, regions for random mutagenesis and in vitro evolution were chosen...
April 14, 2019: Journal of Molecular Biology
Sirawit Ittisoponpisan, Suhail A Islam, Tarun Khanna, Eman Alhuzimi, Alessia David, Michael J E Sternberg
Knowledge of protein structure can be used to predict the phenotypic consequence of a missense variant. Since structural coverage of the human proteome can be roughly tripled to over 50% of the residues if homology-predicted structures are included in addition to experimentally-determined coordinates, it is important to assess the reliability of using predicted models when analysing missense variants. Accordingly, we assess whether a missense variant is structurally damaging by using experimental and predicted structures...
April 14, 2019: Journal of Molecular Biology
H Steven Seifert
No abstract text is available yet for this article.
April 12, 2019: Journal of Molecular Biology
Binu K Sasi, Parshuram J Sonawane, Vinayak Gupta, Bhavani S Sahu, Nitish R Mahapatra
No abstract text is available yet for this article.
April 11, 2019: Journal of Molecular Biology
Jeffrey W Roberts
Bacterial transcription termination, described mostly for E. coli, occurs in three recognized ways: intrinsic termination, an activity only of the core RNAP enzyme and transcript sequences that encode an RNA hairpin and terminal uridine-rich segment; termination by the enzyme Rho, an ATP-dependent RNA translocase that releases RNA by forcing uncharacterized structural changes in the elongating complex; and Mfd-dependent termination, the activity of an ATP-dependent DNA translocase that is thought to dissociate the elongation complex by exerting torque on a stalled RNAP...
April 9, 2019: Journal of Molecular Biology
Shaunak Deota, Sivasudhan Rathnachalam, Kanojia Namrata, Mayank Boob, Amit Fulzele, S Radhika, Shubhra Ganguli, Chinthapalli Balaji, Stephanie Kaypee, Krishna Kant Vishwakarma, Tapas Kumar Kundu, Rashna Bhandari, Anne Gonzalez de Peredo, Mithilesh Mishra, Ravindra Venkatramani, Ullas Kolthur-Seetharam
Cyclin dependent kinase 1 (CDK1) is essential for cell cycle progression. While dependence of CDK activity on cyclin levels is well established, molecular mechanisms that regulate their binding are less understood. Here, we report for the first time that CDK1:cyclin-B binding is not default but rather determined by the evolutionarily conserved catalytic residue, lysine-33 in CDK1. We demonstrate that the charge state of this lysine allosterically remodels the CDK1:cyclin-B interface. Cell cycle dependent acetylation of lysine-33 or its mutation to glutamine, which mimics acetylation, abrogates cyclin-B binding...
April 8, 2019: Journal of Molecular Biology
Kirsten Jung, Sophie Brameyer, Florian Fabiani, Ana Gasperotti, Elisabeth Hoyer
A complex relationship exists between environmental factors, signaling networks and phenotypic individuality in bacteria. In this review, we will focus on the organization, function and control points of multiple-input histidine kinase-based signaling cascades as a source of phenotypic heterogeneity. In particular, we will examine the quorum sensing cascade in Vibrio harveyi and the pyruvate sensor network in Escherichia coli. We will describe and compare these histidine kinase-based signaling networks in terms of robustness, the molecular mechanisms of signal transduction and the role of RNA switches...
April 7, 2019: Journal of Molecular Biology
Jehangir Cama, Abby Mae Henney, Mathias Winterhalter
The double membrane cell envelope of Gram negative bacteria is a sophisticated barrier that facilitates the uptake of nutrients and protects the organism from toxic compounds. An antibiotic molecule must find its way through the negatively charged lipopolysaccharide layer on the outer surface, pass through either a porin or the hydrophobic layer of the outer membrane, then traverse the hydrophilic peptidoglycan layer only to find another hydrophobic lipid bilayer before it finally enters the cytoplasm, where it typically finds its target...
April 5, 2019: Journal of Molecular Biology
Laurence Serre, Virginie Stoppin-Mellet, Isabelle Arnal
End-binding proteins (EBs), referred to as the core components of the microtubule plus-end tracking protein network, interact with the C-terminus of the Adenomatous Polyposis Coli (APC) tumor suppressor. This interaction is disrupted in colon cancers expressing truncated APC. APC and EBs act in synergy to regulate microtubule dynamics during spindle formation, chromosome segregation and cell migration. Since EBs autonomously end-track microtubules and partially co-localize with APC at microtubule tips in cells, EBs have been proposed to direct APC to microtubule ends...
April 5, 2019: Journal of Molecular Biology
Catherine L Tooke, Philip Hinchliffe, Eilis C Bragginton, Charlotte K Colenso, Viivi H A Hirvonen, Yuiko Takebayashi, James Spencer
The β-lactams retain a central place in the antibacterial armamentarium. In Gram-negative bacteria β-lactamase enzymes that hydrolyse the amide bond of the four-membered β-lactam ring are the primary resistance mechanism, with multiple enzymes disseminating on mobile genetic elements across opportunistic pathogens such as Enterobacteriaceae (e.g. Escherichia coli) and non-fermenting organisms (e.g. Pseudomonas aeruginosa). β-lactamases divide into four classes; the active-site serine β-lactamases (SBLs, classes A, C and D) and the zinc-dependent or metallo-β-lactamases (MBLs, class B)...
April 5, 2019: Journal of Molecular Biology
Min Su, Amanda L Erwin, Anne M Campbell, Tasia M Pyburn, Lauren E Salay, Jessica L Hanks, D Borden Lacy, David L Akey, Timothy L Cover, Melanie D Ohi
Helicobacter pylori colonizes the human stomach and contributes to the development of gastric cancer and peptic ulcer disease. H. pylori secretes a pore-forming toxin called vacuolating cytotoxin A (VacA), which contains two domains (p33 and p55) and assembles into oligomeric structures. Using single particle cryo-electron microscopy, we have determined low-resolution structures of a VacA dodecamer and heptamer, as well as a 3.8 Å structure of the VacA hexamer. These analyses show that VacA p88 consists predominantly of a right-handed beta-helix that extends from the p55 domain into the p33 domain...
April 4, 2019: Journal of Molecular Biology
Katherine Y Le, Amer E Villaruz, Yue Zheng, Lei He, Emilie L Fisher, Thuan H Nguyen, Trung V Ho, Anthony J Yeh, Hwang-Soo Joo, Gordon Y C Cheung, Michael Otto
Phenol-soluble modulins (PSMs) are amphipathic, alpha-helical peptides that are secreted by staphylococci in high amounts in a quorum-sensing-controlled fashion. Studies performed predominantly in Staphylococcus aureus showed that PSMs structure biofilms, which results in reduced biofilm mass, while it has also been reported that S. aureus PSMs stabilize biofilms due to amyloid formation. We here analyzed the roles of PSMs in in-vitro and in-vivo biofilms of Staphylococcus epidermidis, the leading cause of indwelling device-associated biofilm infection...
April 4, 2019: Journal of Molecular Biology
Benjamin Y Tischler, Tobias M Hohl
The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i.e., vegetative spores) daily and typically clear these in an asymptomatic manner. In immunocompromised individuals, Aspergillus conidia can germinate into tissue-invasive hyphae, disseminate, and cause invasive aspergillosis. In this review, we first discuss novel concepts in host defense against Aspergillus infections, and emphasize new insights in fungal recognition and signaling, innate immune activation and fungal killing...
April 4, 2019: Journal of Molecular Biology
Diego O Serra, Regine Hengge
The extracellular matrix in macrocolony biofilms of E. coli is arranged in a complex large-scale architecture, with homogenic matrix production close to the surface, whereas zones further below display pronounced local heterogeneity of matrix production, which results in distinct 3D architectural structures. Combining genetics, cryosectioning and fluorescence microscopy of macrocolony biofilms, we demonstrate here in-situ that this local matrix heterogeneity is generated by a c-di-GMP-dependent molecular switch characterized by several nested positive and negative feedback loops...
April 4, 2019: Journal of Molecular Biology
Kristine Freude, Sybille Krauss
No abstract text is available yet for this article.
March 28, 2019: Journal of Molecular Biology
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